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A diabetes clinic gives undocumented children with diabetes access to the care they need to maintain their health with this chronic condition.

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In 2018, Jennifer Boughton, a social worker at Children’s National Hospital, came up with the idea of starting a diabetes clinic for patients whose immigration status prevented them from qualifying for insurance. The idea came about after undocumented children were arriving in the emergency department with high blood sugar and dangerously elevated ketone levels.

Through donations and the employees, who volunteer their time, Boughton’s idea became a reality. In January of 2019, the diabetes center held its first access clinic. The clinic has been open every three months since then for undocumented children with diabetes.

Flyers for the clinic are sent to local schools and organizations to help recruit patients.

In the first year, the patient volume has quadrupled and the hbA1c levels have decreased for patients who attend.

Brynn Marks, M.D., endocrinologist at Children’s National Hospital, was diagnosed with Type 1 diabetes at the age of five years old and knows too well the struggles that may come with managing this chronic condition. After finding the right, knowledgeable provider as a teen, Dr. Marks realized that she wanted to become an endocrinologist and be that resource and support for others with Type 1.

Developments in diabetes technologies, including continuous glucose monitors (CGM) and insulin pumps, hold great promise for improving diabetes control while also improving quality of life for those living with Type 1. However, the pace of development also presents challenges for busy clinicians who must keep up with rapid developments in the field. Dr. Marks is focused on making sure patients and providers have the latest information and training on diabetes technologies with the goal that they can be more effectively used by more people in the real world.

“These diabetes technologies are very important for kids and teens with diabetes because they can help them to live life as normally as possible while affording the freedom they need to just be kids,” says Dr. Marks.

Dr. Marks’ recent research includes a study where she used an app to deliver medical education about diabetes technology. Participants received authentic, case-based scenarios focused on the technologies to help them apply knowledge of these technologies to real-world clinical scenarios involving insulin pumps and CGMs. All of the education was delivered through questions and explanations in an effort to keep the learners engaged with the curriculum. The questions were repeated over 3-4 months to improve learning and long-term knowledge retention. The study showed that knowledge and confidence about these technologies improved and ultimately led to better patient care.

Dr. Marks presented two posters at the International Society for Pediatric and Adolescent Diabetes (ISPAD) meeting in October related to her efforts to make these technologies more accessible:

Experiential Learning in T1D Technology Education: Knowledge of Parents and Clinicians: Dr. Marks enrolled different groups of learners in the diabetes technology curriculum mentioned above, including parents of children with Type 1 diabetes, attending physicians, pediatric endocrine fellows and certified diabetes educators. Results showed minimal difference among those groups in terms of knowledge about the pumps and CGMs. Interestingly, clinicians who had the opportunity to wear the technologies for educational purposes had greater knowledge than clinicians who did not have the same opportunity. Based on these results, Dr. Marks advocated that opportunities to wear pumps and CGMs should be a routine part of education for clinicians working with these technologies.

A Qualitative Analysis of Clinicians’ Experiences Wearing CGM: Dr. Marks explored the reactions of clinicians without diabetes who were given the opportunity to wear continuous glucose monitors for 1 week. Participants reported that the opportunity to wear these technologies improved their knowledge and gave them greater empathy for patients using CGM.

Dr. Marks’ work to date has identified strategies to improve knowledge about insulin pumps and CGM. Moving forward, she will continue to study the best ways to educate parents and clinicians about these diabetes technologies in hopes of improving the day to day lives of the children they care for.

The brain comprises only 2% of the body’s volume, but it uses more than 20% of its energy, which makes this organ particularly vulnerable to changes in metabolism.

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More than 30 million Americans have diabetes, with the vast majority having Type 2 disease. Characterized by insulin resistance and persistently high blood sugar levels, poorly controlled Type 2 diabetes has a host of well-recognized complications: compared with the general population, a greatly increased risk of kidney disease, vision loss, heart attacks and strokes and lower limb amputations.

But more recently, says Nathan A. Smith, MS, Ph.D., a principal investigator in Children’s National Research Institute’s Center for Neuroscience Research, another consequence has become increasingly apparent. With increasing insulin resistance comes cognitive damage, a factor that contributes significantly to dementia diagnoses as patients age.

The brain comprises only 2% of the body’s volume, but it uses more than 20% of its energy, Smith explains – which makes this organ particularly vulnerable to changes in metabolism. Type 2 diabetes and even prediabetic changes in glucose metabolism inflict damage upon this organ in mechanisms with dangerous synergy, he adds. Insulin resistance itself stresses brain cells, slowly depriving them of fuel. As blood sugar rises, it also increases inflammation and blocks nitric oxide, which together narrow the brain’s blood vessels while also increasing blood viscosity.

When the brain’s neurons slowly starve, they become increasingly inefficient at doing their job, eventually succumbing to this deprivation. These hits don’t just affect individual cells, Smith adds. They also affect connectivity that spans across the brain, neural networks that are a major focus of his research.

While it’s well established that Type 2 diabetes significantly boosts the risk of cognitive decline, Smith says, it’s been unclear whether this process might be halted or even reversed. It’s this question that forms the basis of a collaborative Frontiers grant, $2.5 million from the National Science Foundation split between his laboratory; the lead institution, Stony Brook University; and Massachusetts General Hospital/Harvard Medical School.

Smith and colleagues at the three institutions are testing whether changing the brain’s fuel source from glucose to ketones – byproducts from fat metabolism – could potentially save neurons and neural networks over time. Ketones already have shown promise for decades in treating some types of epilepsy, a disease that sometimes stems from an imbalance in neuronal excitation and inhibition. When some patients start on a ketogenic diet – an extreme version of a popular fat-based diet – many can significantly decrease or even stop their seizures, bringing their misfiring brain cells back to health.

Principal Investigator Smith and his laboratory at the Children’s National Research Institute are using experimental models to test whether ketones could protect the brain against the ravages of insulin resistance. They’re looking specifically at interneurons, the inhibitory cells of the brain and the most energy demanding. The team is using a technique known as patch clamping to determine how either insulin resistance or insulin resistance in the presence of ketones affect these cells’ ability to fire.

They’re also looking at how calcium ions migrate in and out of the cells’ membranes, a necessary prerequisite for neurons’ electrical activity. Finally, they’re evaluating whether these potential changes to the cells’ electrophysiological properties in turn change how different parts of the brain communicate with each other, potentially restructuring the networks that are vital to every action this organ performs.

Colleagues at Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and Harvard Medical School, led by Principal Investigator Eva-Maria Ratai, Ph.D., will perform parallel work in human subjects. They will use imaging to determine how these two fuel types, glucose or ketones, affect how the brain uses energy and produces the communication molecules known as neurotransmitters. They’re also investigating how these factors might affect the stability of neural networks using techniques that investigate the performance of these networks both while study subjects are at rest and performing a task.

Finally, colleagues at the Laufer Center for Physical and Quantitative Biology at Stony Brook University, led by Principal Investigator Lilianne R. Mujica-Parodi, Ph.D., will use results generated at the other two institutions to construct computational models that can accurately predict how the brain will behave under metabolic stress: how it copes when deprived of fuel and whether it might be able to retain healthy function when its cells receive ketones instead of glucose.

Collectively, Smith says, these results could help retain brain function even under glucose restraints. (For this, the research team owes a special thanks to Mujica-Parodi, who assembled the group to answer this important question, thus underscoring the importance of team science, he adds.)

“By supplying an alternate fuel source, we may eventually be able to preserve the brain even in the face of insulin resistance,” Smith says.

On Nov. 10, 2019, more than 30 pediatric endocrine physicians and nurse practitioners from Washington, D.C., Maryland and Northern Virginia gathered at Children’s National Hospital to discuss the latest in pediatric endocrinology research.

Organized by Paul Kaplowitz, M.D., Professor Emeritus of Pediatrics, this was the third regional pediatric endocrinology meeting since 2012 and the second held at the hospital. “The meetings are a great opportunity for providers to meet regional colleagues who they may communicate with about patients but rarely see face to face,” explains Dr. Kaplowitz.

The providers spent half a day at Children’s National viewing presentations and connecting with their colleagues. Among the presentations was a talk by new Children’s National faculty member Brynn Marks, M.D., MSHPEd, titled, “Medical Education in Diabetes Technologies.”

The presentation highlighted Dr. Marks’ research on how to best teach providers to make optimal use of the information provided by continuous blood glucose monitoring, as well as how to adjust insulin pump settings based on frequent blood glucose testing.

Another notable presentation was by Richard Kahn, Ph.D., recently retired former chief scientific and medical officer at the American Diabetes Association. Dr. Kahn’s talk was titled “Prediabetes: Is it a meaningful diagnosis?”

“This was an excellent talk whose message was that making a diagnosis of ‘prediabetes’ may not be nearly as helpful as we thought, since most patients tests either revert to normal or remain borderline, and there is no treatment or lifestyle change which greatly reduces progression to type 2 diabetes,” says Dr. Kaplowitz.

“Innovation meets tradition,” is how many attendees and journalists described the American College of Cardiology’s 68th Scientific Sessions (ACC.19), which took place March 16-18, 2019 in New Orleans, La.

Gerard Martin, M.D., F.A.A.P., F.A.C.C., F.A.H.A., a pediatric cardiologist and the medical director of Global Services at Children’s National, supported this narrative by referencing both themes in his 2019 Dan G. McNamara keynote lecture, entitled “Improved Outcomes in Congenital Heart Disease through Advocacy and Collaboration.” Dr. Martin highlighted advancements in the field of pediatric cardiology that took place over the past 15 years, while touting modern advancements – such as pulse oximetry screenings for critical congenital heart disease – that were a result of physician-led advocacy and collaboration.

Dr. Martin’s message was to continue to invest in research and technology that leads to medical breakthroughs, but to remember the power of partnerships, such as those formed by the National Pediatric Cardiology Quality Improvement Collaborative. These alliances, which generated shared protocols and infrastructure among health systems, improved interstage mortality rates between surgeries for babies born with hypolastic left heart syndrome.

A dozen cardiologists and clinicians from the Children’s National Heart Institute also participated in CME panel discussions or delivered poster presentations to support future versions of this template, touching on early-stage innovations and multi-institution research collaborations. The themes among Children’s National Heart Institute faculty, presented to a diverse crowd of 12,000-plus professional attendees representing 108 countries, included:

Personalized guidelines:

Sarah Clauss, M.D., F.A.C.C., a cardiologist, presented “Unique Pediatric Differences from Adult Cholesterol Guidelines: Lipids and Preventive Cardiology,” before Charles Berul, M.D., division chief of cardiology and co-director of the Children’s National Heart Institute, presented “Unique Pediatric Differences from Adult Guidelines: Arrhythmias in Adults with Congenital Heart Disease,” in a joint symposium with the American Heart Association and the American College of Cardiology.

Early detection:

Anita Krishnan, M.D., associate director of the echocardiography lab, presented “Identifying Socioeconomic and Geographic Barriers to Prenatal Detection of Hypoplastic Left Heart Syndrome and Transposition of the Great Arteries” as a moderated poster in Fetal Cardiology: Quickening Discoveries.

Innovation:

Jai Nahar, M.D., a cardiologist, moderated “Future Hub: Augmented Cardiovascular Practitioner: Giving Doctors and Patients a New Voice.” The session focused on technical aspects of artificial intelligence, such as language processing and conversational artificial intelligence, as well as how applications are used in patient-physician interactions.

Nahar also participated in a key event on the Heart-to-Heart stage, entitled “Rise of Intelligent Machines: The Potential of Artificial Intelligence in Cardiovascular Care.”

“While I enjoyed the significant representation of Children’s National faculty at the meeting and all of the presentations this year, one research finding that I found particularly compelling was Dr. Krishnan’s poster about geographical disparities in detecting congenital heart disease,” says Dr. Berul. “Her research finds obstetricians providing care to women in the lowest quartile of socioeconomic areas were twice as likely to miss a diagnosis for a critical congenital heart defect during a fetal ultrasound, compared to obstetricians providing care for women in the highest quartiles.”

Dr. Krishnan’s study was the collaborative effort of 21 centers in the United States and Canada, and investigated how socioeconomic and geographic factors affect prenatal detection of hypoplastic left heart syndrome and transposition of the great arteries.

“We studied over 1,800 patients, and chose these diseases because they require early stabilization by a specialized team at a tertiary care center,” says Dr. Krishnan, who led the research in conjunction with the Fetal Heart Society Research Collaborative. “We hope that by understanding what the barriers are, we can reduce disparities in care through education and community-based outreach.”

Elizabeth Estrada, M.D., was struck by the increasing number of children with obesity and type 2 diabetes when she finished her fellowship in 1996. That fascination, along with increasingly alarming statistics about the rise in type 2 diabetes in youth over the past 20 years, steered her to a career focused on pediatric diabetes and metabolism that eventually led her to Children’s National Health System, where she will become the director of the type 2 diabetes program this spring.

Coming most recently from the University of North Carolina, where she served as Chief of the Division of Pediatric Endocrinology and Diabetes, Dr. Estrada will work closely with Children’s National Endocrinology Division Chief Andrew Dauber, M.D., and Diabetes Services Director Fran Cogen, M.D., to create a multidisciplinary type 2 diabetes care structure that she has seen success with throughout her career.

“Children with type 2 diabetes have very different needs than children with type 1,” Dr. Estrada explains. “They need more nutrition, more social work, and psychological support.”

Children’s National presents Dr. Estrada with a unique opportunity at a time when the field of care and treatment options for children with type 2 diabetes is expanding. She aims to develop a comprehensive, multidisciplinary program integrating the established Children’s National obesity program with the nationally-ranked endocrinology and diabetes team, which has a strong foundation in providing psychological support to families, which is part of a larger toolkit at Children’s National to help families manage a diabetes diagnosis.

The obesity program at Children’s National emphasizes personalized clinical care and education to prevent and reduce the prevalence of obesity, incorporating multiple aspects of medical and surgical care for obese children and adolescents through the Improving Diet, Energy and Activity for Life (IDEAL) clinic and the bariatric surgery program. The IDEAL clinic helps children with dietary counseling, health education classes, physical activity and weight-management techniques, as well as psychosocial support to help children reach and maintain a healthy weight.

One of the first children’s hospitals to be accredited by the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP®) and the only hospital in the area to be accredited to perform bariatric surgery on adolescents, the bariatric surgery program at Children’s National is directed by Evan Nadler, M.D., who has been safely performing surgeries for nearly 15 years.

The American Diabetes Association (ADA) recently published updates to the “Standards of Medical Care in Diabetes,” which provides research-based practice recommendations for children and adolescents with type 2 diabetes, including metabolic surgery as a treatment recommendation, stating:

The results of weight-loss and lifestyle interventions for obesity in children and adolescents have been disappointing, and no effective and safe pharmacologic intervention is available or approved by the U.S. Food and Drug Administration in youth. Over the last decade, weight-loss surgery has been increasingly performed in adolescents with obesity. Small retrospective analyses and a recent prospective multicenter nonrandomized study suggest that bariatric or metabolic surgery may have benefits in obese adolescents with type 2 diabetes similar to those observed in adults.

The recommendations further stipulate that metabolic surgery should only be considered under certain circumstances, including for those adolescents with T2D who are markedly obsess (BMI > 35 kg/m2) and who have uncontrolled glycemia and/or serious comorbidities despite lifestyle and pharmacologic intervention, and it should only be performed by an experienced surgeon working as part of a well-organized and engaged multidiscipinary team.

Working closely with Dr. Nadler and the obesity team will be a hallmark of Dr. Estrada’s role.

Her goal is to organize a clinic that not only provides clinical care and surgical options, but also includes research and provides medical education and training to medical students, residents and fellows. Dr. Estrada’s own research has focused on insulin resistance, one of the underlying problems in type 2 diabetes.

“There are several clinical trials currently exploring the efficacy and safety of medications for type 2 diabetes in children, something that is incredibly important since Metformin and insulin are the only approved options at this point,” Estrada says. “It is imperative that we bring research to Children’s National as a complement to the existing programs and to continue providing the highest level of care for these patients.”

https://innovationdistrict.childrensnational.org/wp-content/uploads/2019/03/Elizabeth-Estrada.png400300Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2018/11/idlogo1-tagline-Advances-in-Medicine.gifInnovation District2019-03-26 13:40:192019-05-08 13:20:01A new type 2 diabetes program leader in a time of change

The iLet bionic pancreas helps patients manage their diabetes by both monitoring blood glucose levels and administering insulin and glucagon.

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Children’s National Health System has been selected to participate in a multi-center clinical trial to test the efficacy of the iLet bionic pancreas — a device that automatically regulates blood sugar levels in patients with Type 1 diabetes.

Patients generally manage diabetes by constantly monitoring their blood sugar levels and administering insulin when necessary. Unfortunately, too much insulin can cause hypoglycemia, or low blood sugar, which can result in hypoglycemic seizures, coma or rarely, death. Thus, it is extremely important for people with diabetes to regulate their insulin dosages and maintain their blood sugar levels within a range decided by the family and diabetes team.

“The burden of caring for diabetes on a daily basis is grueling,” says Seema Meighan, FNP, a nurse practitioner involved in the upcoming clinical trial. “It is by far one of the most challenging chronic diseases to manage, and requires vigilant participation 100 percent of the time to stay well controlled.”

“In a traditional infusion pump, patients only have access to insulin to control glucose levels,” explains Meighan. “This can become problematic when it comes to hypoglycemia. The hope with a bi-hormonal system is that glucagon can be delivered during times that the glucose is low in order to stabilize levels without user interaction.”

Developed at Boston University by Edward Damiano, Ph.D., and Firas El-Khatib, Ph.D., the iLet is a hand-held device about the size of an iPhone but twice as thick, and can easily fit into a pocket. The unit consists of a dual chamber infusion pump that can be configured to deliver only insulin, only glucagon or both hormones. The device uses a wireless glucose sensor on the patient’s body to test blood sugar levels every five minutes. It then determines which hormone is needed and administers it via catheters connected to the patient.

In short-term studies, the iLet was able to maintain blood glucose levels close to normal in both adults and children in carefully controlled environments.

In 2016, the Children’s National Health System Division of Endocrinology and Diabetes, led by diabetologist Fran Cogen, M.D., C.D.E., was one of several pediatric sites that were selected to participate in pivotal clinical trials to further test the efficacy of the bionic pancreas. Later this year, the team at Children’s National will begin enrolling five to 10 children to test iLet devices that only deliver insulin. Once these initial studies are completed, the team will perform an additional trial to test iLet devices configured to deliver both insulin and glucagon.

“This trial is important as it represents the first dual chamber pump to manage glucose levels,” says Meighan. “It could potentially change the way we treat diabetes entirely. It represents a hope to our patients and families that one day this disease will have far less of a daily burden than it currently does.”

Study findings offer hope to the nearly 2 billion adults who are overweight or obese worldwide that detrimental effects of carrying too much weight can recede. (Image source: Centers for Disease Control and Prevention)

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Losing weight appears to reset the chemical messages that fat cells send to other parts of the body that otherwise would encourage the development of Type 2 diabetes, substantially reducing the risk of that disease, a team led by Children’s National Health System researchers report in a new study. The findings offer hope to the nearly 2 billion adults who are overweight or obese worldwide that many of the detrimental effects of carrying too much weight can recede, even on the molecular level, once they lose weight.

In 2015, Robert J. Freishtat, M.D., M.P.H., Chief of Emergency Medicine at Children’s National and Associate Professor of Pediatrics, Emergency Medicine and Integrative Systems Biology at The George Washington University School of Medicine & Health Sciences, and colleagues showed that fat cells (also known as adipocytes) from people who are obese send messages to other cells that worsen metabolic function. These messages are in the form of exosomes, nanosized blobs whose contents regulate which proteins are produced by genes. Exosomes are like “biological tweets,” Dr. Freishtat explains — short signals designed to travel long distances throughout the body.

Dr. Freishtat’s earlier research showed that the messages contained in exosomes from patients who are obese alter how the body processes insulin, setting the stage for Type 2 diabetes. However, says Dr. Freishtat, it has remained unclear since that publication whether these aberrant messages from adipocytes improve after weight loss.

“We’ve known for a long time that too much adipose tissue is bad for you, but it’s all moot if you lose the weight and it’s still bad for you,” he explains. “We wanted to know whether these negative changes are reversible. If you reduce fat, does the disease risk that goes along with excess fat also go away?”

Details of the study

To investigate this question, Dr. Freishtat and colleagues worked with six African American adults scheduled to receive gastric bypass surgery — a nearly surefire way to quickly lose a large amount of weight. The volunteers, whose average age was 38 years, started out with an average body mass index (BMI) of 51.2 kg/m2. (The Centers for Disease Control and Prevention considers a healthy BMI to range between 18.5 to 24.9.)

Two weeks before these volunteers underwent surgery, researchers collected blood samples and took a variety of measurements. The researchers then performed a repeat blood draw and measurements one year after the surgery took place, when the volunteers’ average BMI had dropped to 32.6.

Dr. Freishtat and colleagues drew out the adipocyte-derived exosomes from both sets of blood samples and analyzed their contents. The team reports in the January 2017 issue of Obesity that at least 168 microRNAs — the molecules responsible for sending specific messages — had changed before and after surgery. Further analyses showed that many of these microRNAs were involved in insulin signaling, the pathways that the body uses to regulate blood sugar. By changing these outgoing microRNAs for the better, Dr. Freishtat says, adipocytes actively were encouraging higher insulin sensitivity in other cells, warding off Type 2 diabetes.

Sure enough, each volunteer had better insulin sensitivity and other improved markers of metabolic health post-surgery, including lower branched chain amino acids and a two-fold reduction in their glutamate to glutamine ratio.

“These volunteers were essentially cured of their diabetes after surgery. The changes we saw in their surgery-responsive microRNAS correlated with the changes we saw in their metabolic health,” Dr. Freishtat says.

A glimpse into the future

Dr. Freishtat and colleagues plan to study this phenomenon in other types of weight loss, including the slower and steadier paths that most individuals take, such as improving diet and doing more exercise. The team expects to see similar changes in exosomes of patients who lose weight in non-surgical ways.

By further examining the aberrant messages in microRNAs being sent out from adipocytes, he says, researchers eventually might be able to develop treatments to reverse metabolic problems in overweight and obese patients before they lose the weight, improving their health even before the often challenging process of weight loss begins.

“Then, if you can disrupt this harmful signaling in combination with weight-loss strategies,” Dr. Freishtat says, “you’re really getting the best of both worlds.”

Eventually, he adds, tests might be available so that doctors can warn patients that their fat cells are sending out harmful messages before disease symptoms start. By giving patients an early heads up, Dr. Freishtat says, patients might be more likely to heed advice from physicians and make changes before it’s too late.

“If doctors could warn patients that their fat is telling their blood vessels to fill up with plaque and trigger a heart attack in 10 to 20 years,” he says, “patients might be more compliant with treatment regimens.”

New research shows the effectiveness of an Advance Care Planning model developed through participatory research with adolescents in improving palliative care among adult people living with #HIV
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